Ketonal injections are an effective drug for pain relief

Ketonal injections are a popular medication in the complex treatment of diseases of the musculoskeletal system. The medicine belongs to the group of non-steroidal anti-inflammatory drugs. The solution in ampoules is used for intramuscular and intravenous administration.

Composition and indications

The main active ingredient in the drug is ketoprofen. Ketonal ampoules contain 2 ml of solution with 100 mg of active substance. The injection liquid may be clear or have a slightly yellowish tint.

Ketoprofen has anti-inflammatory, analgesic and antipyretic properties. It is quickly absorbed from the gastrointestinal tract, which causes quick results.

Ketonal injections are indicated in the treatment of various diseases for the symptomatic treatment of disease processes. They are most effective for relieving pain that accompanies inflammatory and degenerative diseases of the musculoskeletal system.

Ketonal injections, the instructions for use confirm this, improve the condition of rheumatoid and seronegative arthritis during exacerbation of diseases when severe pain occurs.

For symptomatic treatment, the drug is also prescribed:

• For gout. With the development of this disease, uric acid salts are deposited in the joints, which causes their modification and severe pain. Ketonal injections are indicated to relieve an attack of gout, which is characterized by swelling in the area of ​​one of the joints and pressing pain in it.
• For osteoarthritis. As a rule, the cause of the pathology is damage to the joint or an inflammatory process in it. Ketonal injections can relieve pain and maintain joint mobility.

Ketonal injections are prescribed to relieve post-traumatic and postoperative pain syndrome. Thanks to its pronounced analgesic properties, the drug improves the condition of cancer, algodisminorrhea, and inflammation of the pelvic organs. It can be used to relieve severe headaches caused by various reasons, as well as in other pathological conditions:

• Migraine.
• Myalgia.
• Bursitis.
• Radiculitis.
• Neuralgia.

Ketoprofen in the treatment of acute and chronic pain: review of literature data

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most important class of drugs used to relieve acute and control chronic pain in therapeutic practice. NSAIDs are distinguished by a combination of analgesic, anti-inflammatory and antipyretic effects, which provides them with an advantage over paracetamol and opioids [1–3].

Currently, nineteen different NSAIDs are registered in Russia. These are “international nonproprietary names,” i.e., chemical substances, and there are an order of magnitude more specific commercial drugs. Unfortunately, none of the modern NSAIDs can be considered ideal: if any drug has an advantage in one or another parameter, most likely, it also has serious disadvantages.

The main difference between different representatives of the NSAID group is their safety. Until recently, the main problem with these drugs was the development of complications from the gastrointestinal tract (GIT). All NSAIDs are cyclooxygenase (COX) 2 inhibitors, however, in addition to this action, they can inhibit the structurally similar enzyme COX-1. The work of the latter is necessary to maintain the protective potential of the gastrointestinal mucosa, so its blockade can lead to the development of dangerous gastrointestinal pathology - the so-called. NSAID gastropathy and NSAID enteropathy [4].

Selectivity for COX-2, and therefore the risk of developing gastrointestinal pathology, became the basis for dividing NSAIDs into two groups: “traditional” or non-selective (n-NSAIDs) and selective (s-NSAIDs). s-NSAIDs, so-called. “coxibs” were created in the late 90s of the last century as a safer alternative to “traditional” NSAIDs for the gastrointestinal tract. But, as it turned out, “coxibs” have a serious drawback: selective blockade of COX-2 can disrupt the balance of factors affecting blood clotting - the synthesis of thromboxane A2 and prostacyclin, which determines the prothrombotic effect. In patients with diseases of the cardiovascular system (CVS), this is fraught with an increased risk of thromboembolic complications, such as myocardial infarction (MI) and ischemic stroke [4].

This problem has renewed interest among practitioners in “traditional” NSAIDs, the use of which seemed to be associated with a significantly lower risk of cardiovascular (CV) complications.

But not all n-NSAIDs are safe against cardiovascular disease. Thus, the risk of CV complications when using the most popular representative of the “traditional” NSAIDs in Russia, diclofenac, is very high. This fact is shown by a meta-analysis of 25 population-based studies conducted in 18 independent populations and representing the individual risk of CV complications for different NSAIDs. The outcome measure was the incidence of myocardial infarction, which occurred in ~100,000 patients. Minimal risk of MI was shown for naproxen (odds ratio (OR) 1.06) and celecoxib (OR 1.12); for diclofenac this figure was 1.38 [5].

Another popular n-NSAID, ketoprofen, demonstrates a significantly lower risk of LE complications. This drug appeared in Europe in 1971 and quickly gained a reputation as an effective and reliable analgesic [6]. Over forty years of clinical use, it has not lost its significance. P. Sarzi-Puttini et al. emphasize this fact in a review with a very characteristic title: “Pain and ketoprofen: its role in clinical practice,” which was published in 2010. They point to a huge base of evidence of its effectiveness, a wide range of indications - in fact, all pathological processes accompanied by nociceptive pain, and a good reputation among doctors [7].

Interest in ketoprofen can be assessed by the increase in its prescriptions in European countries. Thus, M. Venegoni et al. showed that, against the backdrop of a small but clear decrease in overall sales of “prescription” NSAIDs in Italy for the period from 2006 to 2009. the popularity of ketoprofen has almost doubled (by 93%). If in 2006 263,897 residents of this country purchased ketoprofen, then in 2009 - already 508,699 [8].

Many experts associate the high analgesic potential of ketoprofen with the characteristics of its molecule. The lipophilicity and relatively small size of ketoprofen determine its ability to easily penetrate into inflamed tissue (for example, into the synovial cavity in arthritis), creating a high concentration [7, 9]. Great importance is attached to the diffusion of ketoprofen through the blood-brain barrier and its effect on the central structures of the pain system. Experimental data confirm the equilibrium concentration of the unbound fraction of ketoprofen in blood plasma and cerebrospinal fluid. Moreover, the central effect of this drug is associated not only with the blockade of COX-2, but also with other mechanisms, in particular, with its effect on the serotonergic antinociceptive system [10].

As noted above, the experience of using ketoprofen includes all diseases and pathological conditions for which the prescription of NSAIDs seems appropriate. Working with ketoprofen is facilitated by the availability of a full range of dosage forms: solution for intravenous (IV) and intramuscular (IM) administration, standard tablets, controlled-release capsules, forms for topical use, rectal suppositories.

Ketoprofen is a very successful remedy for urgent pain relief. In 2009, data from a Cochrane meta-analysis were published evaluating the results of a single dose of ketoprofen at a dose of 25–100 mg for acute postoperative pain. The material was based on data from 14 randomized controlled trials (RCTs) (968 patients treated with ketoprofen, 520 placebo), and the main evaluation criterion was a pain reduction > 50% for a period of 4 to 6 hours. The researchers used the NNT (number need to treat) index, which shows the number of patients who need to be treated to achieve a significant difference from placebo. This index was 2.4–3.3, which shows a fairly high effectiveness of the drug [11].

Data from a large-scale study (n = 338) were recently published, which examined the effect of a single intravenous administration of parecoxib 40 mg and ketoprofen 100 mg for the relief of acute renal colic. Ketoprofen, which acted as a comparison drug, was in no way inferior to the representative of “coxibs”: the reduction in pain (on a visual analogue scale - VAS) 30 minutes after injection was 35.2 ± 26.0 and 33.8 ± 24.6 mm [12 ].

The work of S. Karvonen et al. is an example of the successful use of ketoprofen in surgical practice. Here, ketoprofen at a dose of 300 mg/day was used in 60 patients who had undergone orthopedic surgery. The control group consisted of patients receiving placebo or paracetamol 4 g/day. The criterion for effectiveness, in addition to reducing the severity of pain, was the assessment of the “opioid-sparing” effect, which was determined by comparing the dose of fentanyl required for persistent analgesia. This effect was noted only in the ketoprofen group: the average dose of fentanyl was 22% less than in the placebo group and 28% less than in the paracetamol group [13].

Good results have been observed when using ketoprofen in dentistry. J. Olson N. et al. conducted a study in which 239 patients were prescribed a minimum dose of ketoprofen (25 mg), ibuprofen 400 mg or paracetamol 1000 mg after extraction of the 3rd molar; The “passive” control was placebo. The main evaluation method was to compare the number of patients who were completely free of pain 6 hours after tooth extraction. This result was achieved in almost all patients who received ketoprofen - 99%, in 96% of those who received ibuprofen and 88% - paracetamol (the difference is not significant). All active drugs were superior to placebo, which relieved pain in only one third of patients (33.6%). As can be seen, even a minimal dose of ketoprofen provides the same pronounced (and even slightly greater) pain relief as standard therapeutic doses of ibuprofen and paracetamol [14].

A successful demonstration of the benefits of ketoprofen was the work of I. Jokhio et al., who compared it with diclofenac in 180 patients experiencing severe pain (average VAS value ~70 mm) due to trauma or acute soft tissue pathology of a rheumatic nature. In this case, the so-called “stepped” therapy: on the first day, NSAIDs were administered as intramuscular injections and then orally. Accordingly, half of the patients received two injections of ketoprofen 100 mg each, and then took this drug 100 mg 2 times a day. The second group of patients received two injections of diclofenac 75 mg, and subsequently took it 50 mg 3 times a day orally. The course of treatment was 2 weeks. By the end of the observation period, ketoprofen showed better results (Fig. 1). At the same time, 72% of patients receiving ketoprofen rated its tolerability as “good or excellent”; Only 50% of patients gave this assessment to diclofenac [15].

One of the latest evidence of the high analgesic effectiveness of ketoprofen was the work of Italian scientists P. Sarzi-Puttini et al. — a meta-analysis of 13 RCTs (n = 898), which compared the effect of ketoprofen 50–200 mg/day with ibuprofen 600–1800 mg/day or diclofenac 75–100 mg/day in patients with various rheumatic diseases. Ketoprofen showed significant superiority over comparator drugs in 9 of 13 RCTs. Moreover, the likelihood of achieving a favorable effect when prescribing ketoprofen was almost 2 times higher (OR 0.459: 0.33–0.58, p = 0.000) [16].

Ketoprofen has proven to be an effective remedy for relieving a migraine attack. According to the results of a study by M. Dib et al., it was not inferior to zolmitriptan, a representative of the group of triptans, which are the most important pathogenetic agent for the treatment of this disease. In this study, 235 patients with migraine took a single dose of ketoprofen 75 or 150 mg or zolmitriptan. All groups showed almost the same result: after 2 hours, pain stopped in 62.6%, 61.6% and 66.8% of patients, respectively [17].

It should be noted that ketoprofen has good anti-inflammatory potential. The best model for assessing the anti-inflammatory effect of NSAIDs is the relief of gouty arthritis, in which severe pain is determined by an acute inflammatory response. Indomethacin, which has pronounced anti-inflammatory properties, has long been considered the “gold standard” for the treatment of this pathology. Ketoprofen, as shown by R. Altman et al., was successfully compared with this drug. In the study, 59 patients with acute gouty arthritis took ketoprofen 100 mg 3 times a day or indomethacin 50 mg 3 times a day for 7 days. Ketoprofen provided significant pain relief on the first day of treatment in 92% of patients; in the control group they were 91%. After a week of treatment, the attack was completely stopped in 24% and 22% of patients. As can be seen, ketoprofen was not inferior to indomethacin in effectiveness. But at the same time, it was clearly superior in safety - while taking indomethacin, any side effects were noted in 20% of patients, and in the ketoprofen group - only in 11% [18].

In addition to emergency pain relief, ketoprofen has proven to be effective for long-term pain control in chronic musculoskeletal diseases.

Important evidence of the merits of ketoprofen was a European prospective open study that included about 20 thousand patients with various rheumatic pathologies, mainly osteoarthritis (OA). After 1 month, more than 70% of patients taking ketoprofen at a dose of 200 mg/day reported good or excellent results; At the same time, gastrointestinal complications occurred in a total of 13.5%, and ulcers and bleeding in only 0.03% [19].

The work of M. Schattenkirchner et al. showed good tolerability of ketoprofen with long-term use. In their study, 823 patients with OA and rheumatoid arthritis received ketoprofen for a year. During treatment, complications from the gastrointestinal tract occurred in 28% of patients (only 1.7% were serious), and from the cardiovascular system - in 3.2%, which is relatively small, given the predominantly elderly age of the patients and severe comorbid background [20].

Successful results were obtained when using ketoprofen in patients with ankylosing spondylitis (AS). In AS, NSAIDs play the role of the main therapeutic agent to control the progression of the disease. In a study by M. Dougados et al. 246 patients with AS took celecoxib 200 mg, ketoprofen 200 mg or placebo for 6 weeks. There was no significant difference in the analgesic effect of both NSAIDs, although they were significantly superior to placebo. Of particular interest is the effect of NSAIDs on symptoms such as night pain and morning stiffness, which largely reflect an anti-inflammatory effect. The effects of ketoprofen and celecoxib were practically the same: the reduction in night pain averaged 21 and 27 mm VAS (in the placebo group it increased by 13 mm), morning stiffness decreased by 16 and 17 minutes (it did not change in the placebo group). Thus, ketoprofen has a clear anti-inflammatory effect in AS. Interestingly, the number of gastrointestinal complications while taking coxib and ketoprofen did not differ: they occurred in 13% and 14% of patients (8% on placebo) [21]. When discussing the safety of ketoprofen, one cannot ignore the fact that a number of population-based studies demonstrate a significant risk of gastrointestinal complications for this drug. Thus, J. Castellsague et al. conducted a meta-analysis of 28 epidemiological studies (1980–2011), which assessed the development of gastrointestinal complications when using various NSAIDs. The lowest risk was observed for celecoxib - OR 1.45, aceclofenac 1.4 and ibuprofen - 1.84. The danger was significantly higher when using diclofenac - 3.34, meloxicam - 3.47 and nimesulide - 3.83. Ketoprofen was among the top three drugs with the highest risk - 3.92, as well as naproxen - 4.1 and indomethacin - 4.14 [22].

On the other hand, one of the largest population studies showed a relatively low risk of gastrointestinal complications for ketoprofen. This work by Finnish scientists A. Helin-Salmivaara et al., based on an assessment of the causes of 9191 cases of gastrointestinal bleeding, ulcers and perforation, noted from 2000 to 2004. The control group consisted of 41,780 individuals matched by gender and age. The risk of gastrointestinal complications when using ketoprofen was lower compared to diclofenac: OR 3.7 and 4.2, respectively. Interestingly, ketoprofen showed a similar or even lower risk of developing gastrointestinal pathology than more selective NSAIDs (with the exception of celecoxib). Thus, the OR for meloxicam, nimesulide and etoricoxib was 3.4, 4.0 and 4.4, respectively [23].

It should be noted that Russia has accumulated extensive experience in the use of ketoprofen. In particular, a number of clinical studies were conducted in our country, the results of which showed not only the good therapeutic potential of this drug, but also a low incidence of complications [24, 25].

Among them, the work of L. B. Lazebnik et al. should be highlighted, in which a 3-month comparison of 4 NSAIDs: lornoxicam, nimesulide, celecoxib and ketoprofen was carried out in 132 patients with OA. The authors studied the risk of gastrointestinal complications and daily dynamics of blood pressure (BP). Ketoprofen demonstrated good tolerability: the number of patients with erosions and ulcers after using lornoxicam was 66% (!), nimesulide - 13.5%, ketoprofen - 13.0%, celecoxib - 8.3%. Increased blood pressure over 130/90 mm Hg. Art. was noted in only 2% of patients receiving ketoprofen. With regard to lornoxicam and nimesulide, the situation was completely different: in patients taking these drugs, an increase in blood pressure was noted in 11% and 13% [26] (Fig. 2). This work shows one of the most valuable advantages of ketoprofen - the relatively low risk of cardiovascular complications.

The association between ketoprofen use and CV accidents has been determined in several epidemiological studies. Thus, the low risk of MI when using ketoprofen was shown by American scientists G. Singh et al. Having analyzed the causes of 15,343 episodes of myocardial infarction (61,372 people constituted the corresponding control), the authors compared the frequency of this complication in people taking NSAIDs. It turned out that taking ketoprofen was associated with the lowest risk of MI (OR 0.88), even in comparison with naproxen (OR 1.08), which is traditionally considered the safest drug in relation to CV events [27].

Similar results were obtained by M. Solomon et al., who compared the use of various NSAIDs in 4425 patients who developed MI and 17,700 individuals without this complication. According to the data obtained, there was no difference in the intake of ketoprofen in these groups: 53 patients who developed MI (1.2%) and 190 control subjects (1.1%) received it. Thus, the use of ketoprofen, according to this study, did not increase the risk of developing HF accidents [28].

A low risk of CV complications for ketoprofen was also shown by the results of a population study by Finnish scientists A. Helin-Salmivaara et al. Their work was based on a comparison of data on NSAID use in 33,309 post-MI patients and 138,949 healthy people. It turned out that taking ketoprofen did not actually increase the risk of developing HF accidents (OR 1.11) [29].

In 2012, a large-scale study was published by scientists from Taiwan who studied the CV risk when using various NSAIDs in their own population. The study material was obtained using data from the national health system, which had information on 13.7 million people who used NSAIDs, of whom 8354 had a myocardial infarction. Oral ketoprofen showed minimal risk (OR 1.17). It was found to be safer than the vast majority of other NSAIDs (Figure 3).

It should be noted that parenteral use of NSAIDs (this was a separate section of the analysis) was associated with a higher risk of LE complications. Thus, for ketoprofen the risk was more than doubled: OR 2.34; a similar value was obtained for diclofenac: 1.88, and a significantly higher value for ketorolac: 4.27 [30].

Thus, ketoprofen is a universal analgesic that can be successfully used for both acute and long-term control of chronic pain. Favorable pharmacological properties determine its advantages in comparison with other NSAIDs for urgent pain relief, when the speed of relief of suffering is of fundamental importance. The presence of different dosage forms in the doctor’s arsenal helps when choosing an analgesic therapy strategy: to obtain the fastest possible effect in the first days of treatment, the use of parenteral forms of ketoprofen may be justified, followed by a transition to regular oral administration. A positive point is also the presence on the pharmacological market of high-quality and inexpensive generics of ketoprofen, such as Flamax® (Sotex), available to most patients.

Of course, ketoprofen is not without its drawbacks; the main one, typical of all “traditional” NSAIDs, is the possibility of developing gastrointestinal pathology. However, careful consideration of risk factors before prescribing NSAIDs and, if relevant factors are present, prophylactic use of gastroprotectors (proton pump inhibitors) can significantly reduce this danger. But at the same time, ketoprofen shows a low risk of complications from the cardiovascular system. This is an undoubted advantage that expands the possibility of using this drug in elderly people, many of whom have cardiovascular risk factors.

Literature

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14. J. Olson N., Otero A., Marrero I. et al. Onset of analgesia for liquigel ibuprofen 400 mg, acetaminophen 1000 mg, ketoprofen 25 mg, and placebo in the treatment of postoperative dental pain // Clin Pharmacol. 2001, 41(11): 1238–1247.
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16. Sarzi-Puttini P., Atzeni F., Lanata L., Bagnasco M. Efficacy of ketoprofen vs. ibuprofen and diclofenac: a systematic review of the literature and meta-analysis // Clin Exp Rheumatol. 2013 Sep-Oct; 31 (5): 731–8. Epub 2013 May 17.
17. Dib M., Massiou H., Weber M. et al. Efficacy of oral ketoprofen in acute migraine: a double-blind randomized clinical trial // Neurology. 2002, 58(11): 1660–1665.
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A. E. Karateev, Doctor of Medical Sciences, Professor

FSBI NIIR named after. V. A. Nasonova RAMS, Moscow

Contact Information

Contraindications

A contraindication to ketonal injections is hypersensitivity to the active ingredient or other non-steroidal anti-inflammatory drugs, as well as salicylates.

It is prohibited to use ketonal injections in many other cases. All of them are indicated in the instructions for use of the drug. Injections with the drug are not prescribed until the age of 15 years, in the third trimester of pregnancy and during lactation.

Main contraindications of the drug:

• Exacerbation of peptic ulcer of the stomach and duodenum.
• Heart, liver and kidney failure.
• Blood clotting disorders.

You should stop using the drug if you are diagnosed with Crohn's disease and ulcerative colitis, or if you suspect gastrointestinal or other bleeding. Ketonal injections are not prescribed; the instructions warn about this after coronary artery bypass surgery.

KETOPROFEN

special instructions

You should not combine Ketoprofen with other NSAIDs and/or COX-2 inhibitors.
With long-term use of NSAIDs, it is necessary to periodically evaluate a clinical blood test, monitor kidney and liver function, especially in elderly patients (over 65 years), and conduct a stool test for occult blood.

It is necessary to be careful and monitor blood pressure more often when using the drug Ketoprofen to treat patients with arterial hypertension and cardiovascular diseases that lead to fluid retention in the body. If the condition worsens, you must stop taking the drug.

If visual disturbances occur, use of Ketoprofen should be stopped immediately.

Like other NSAIDs, ketoprofen can mask the symptoms of infectious and inflammatory diseases. If you notice signs of infection or deterioration in health while using the drug, you should immediately consult a doctor.

In patients simultaneously taking antiplatelet agents, anticoagulants, and glucocorticosteroids, the risk of developing gastrointestinal bleeding and ulceration increases.

If there is a history of contraindications from the gastrointestinal tract (bleeding, perforation, peptic ulcer), long-term therapy and the use of high doses of Ketoprofen, the patient should be under close medical supervision. If gastrointestinal bleeding or ulcerative lesions occur, use of Ketoprofen should be discontinued. The use of ketoprofen is contraindicated in patients with a history of gastrointestinal diseases (ulcerative colitis, Crohn's disease), since exacerbation of these diseases is possible. Like other NSAIDs, ketoprofen may inhibit platelet aggregation and increase bleeding time by inhibiting prostaglandin synthesis. In this regard, the use of Ketoprofen in patients simultaneously taking drugs that affect the hemostatic system (for example, warfarin, coumarin derivatives, heparins) is not recommended.

The use of some NSAIDs may be associated with a risk of arterial thrombosis (myocardial infarction, stroke). There is insufficient data to exclude such a risk for ketoprofen.

Like other NSAIDs, ketoprofen can lead to increased concentrations of creatinine and nitrogen in the blood plasma. Like other prostaglandin synthesis inhibitors, Ketoprofen can have a negative effect on the urinary system, which can lead to the development of glomerulonephritis, interstitial nephritis, papillary necrosis, nephrotic syndrome and acute renal failure. Due to the important role of prostaglandins in maintaining renal blood flow, special caution should be exercised when using Ketoprofen in the treatment of patients with cardiac or renal failure, as well as elderly patients taking diuretics, and patients who have a decrease in circulating blood volume for any reason. .

The use of Ketoprofen should be discontinued before major surgery.

As with the use of other NSAIDs, during therapy with Ketoprofen, a slight transient increase in the activity of “liver” transaminases may be observed. In case of a significant increase in the corresponding indicators, the use of the drug should be discontinued.

Ketoprofen should be used with caution in patients with uncontrolled arterial hypertension, coronary heart disease, congestive heart failure, peripheral arterial disease and/or cerebrovascular disease. Patients with risk factors for developing cardiovascular diseases (arterial hypertension, dyslipidemia, diabetes mellitus, smoking) should also use Ketoprofen with caution.

Ketoprofen can affect female fertility, so patients with infertility (including those undergoing examination) are not recommended to use the drug.

There is evidence of rare cases of skin reactions (such as exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis) with the use of NSAIDs. At the first manifestations of a skin rash, damage to the mucous membranes or other signs of an allergic reaction, you should immediately stop taking Ketoprofen and consult a doctor.

Use during pregnancy

According to studies, ketaprofen can have a negative effect on the general course of pregnancy and provoke spontaneous abortion. In addition, when taking the drug there is a risk of developing intrauterine pathologies of the fetus. At the same time, the likelihood of negative consequences for the mother and unborn child increases depending on the dose and duration of use of the drug.

Ketanol injections are prescribed in the first and second trimesters only in cases where the benefits to the woman outweigh the possible risks to the fetus. In this case, the minimum effective dose is indicated, which is taken in a short course.

Absolute contraindications to taking the drug in the third trimester are explained by the fact that ketanol injections can lead to the possible development of weakness of the uterus and other pathological conditions. In addition, even small doses of the drug during this period of pregnancy can increase the duration of bleeding and have a negative effect on the fetus. The use of ketanol injections during lactation is attributed to the fact that studies on whether ketaprofen gets into breast milk and its effect on the child have not been conducted.

Ketoprofen film-coated tablets 100 mg 20 pcs. In Ekaterinburg

Pharmacological action: Inhibits the activity of COX-1 and COX-2, inhibits the synthesis of PG and LT. It has anti-bradykinin activity, stabilizes lysosomal membranes and delays the release of enzymes from them that contribute to tissue destruction during chronic inflammation. Reduces the release of cytokines, inhibits the activity of neutrophils.

The anti-inflammatory effect occurs by the end of 1 week of use. The lysine salt of ketoprofen has equally pronounced anti-inflammatory, analgesic, and antipyretic effects.

In case of articular syndrome, it relieves pain in the joints at rest and during movement, reduces morning stiffness and swelling of the joints, and helps to increase the range of movements.

When taken orally, it is absorbed quickly and quite completely, bioavailability is about 90%. Cmax in the blood is achieved 0.5–2 hours after oral administration, 1.4–4 hours after rectal administration, 15–30 minutes after parenteral administration, and 5–8 hours after application to the skin. When taking retardated forms, the minimum effective concentration is determined after 2–3 hours, Cmax is usually achieved within 6–7 hours. When taken simultaneously with food, the total bioavailability (AUC) does not change, the rate of absorption slows down (for both regular and retardated forms) . Absorption is accompanied by a “first pass” effect through the liver. Binding to blood plasma proteins, mainly albumin - 99%. Equilibrium plasma concentrations are achieved 24 hours after the start of regular use. Easily passes through histohematic barriers and is distributed in tissues and organs. It does not penetrate the BBB in significant quantities. The level of ketoprofen in the synovial fluid is lower than in the blood, but remains within therapeutic limits for a longer time (6–8 hours). Metabolized in the liver by glucuronidation. It is excreted primarily by the kidneys - 80% within 24 hours, mainly in the form of a glucuronic derivative. T1/2 - (2.05±0.58) hours after i.v. administration; 2–4 hours after oral administration in the usual dosage form at a dose of 200 mg; (5.4±2.2) hours after taking the retarded form at a dose of 200 mg. In renal failure, excretion slows down.

Lysine salt of ketoprofen: Tmax after oral administration in the form of granules - 15 minutes, with parenteral administration - 20-30 minutes, with rectal administration - 45-60 minutes. When taken in the form of delayed-release capsules, the effective concentration is achieved within 20–30 minutes and persists for 24 hours.

Therapeutic concentration in synovial fluid persists for 18–20 hours. Metabolized by microsomal liver enzymes. Excreted by the kidneys, 60–80% in the form of glucuronide in 24 hours.

In elderly patients, plasma and renal clearance are reduced, the values ​​of Cmax, AUC and unbound fraction increase with increasing age (more in women than in men).

With cutaneous application, slow transdermal absorption of ketoprofen occurs, which ensures that its concentration in inflamed tissues is maintained within a therapeutic level for a long time. Penetrates well into synovial fluid and connective tissue. Absorption into the systemic circulation is insignificant, bioavailability for gel and spray is about 5%.

When using a solution for topical use (rinse solution) at a dose of 160 mg, Tmax is 1 hour, Cmax value is 350 mg/ml (4% of the concentration obtained by oral administration of 80 mg).

Carcinogenicity, mutagenicity, effect on fertility

Chronic toxicity studies in mice when administered orally (up to 32 mg/kg/day, 96 mg/m2/day, approximately 0.5 MRDC) did not reveal the carcinogenic effect of ketoprofen. In a two-year carcinogenicity study in rats at doses up to 6 mg/kg/day (36 mg/m2/day), no adverse oncogenic effects were detected. Moreover, animals in all groups received drugs for 104 weeks, with the exception of females who received 6 mg/kg/day (36 mg/m2/day) for 81 weeks due to low survival. Survival rate in groups receiving drugs for 104 weeks was 6% compared to the control group.

The mutagenicity of ketoprofen was not detected in the Ames test. When ketoprofen was administered to male rats (up to 9 mg/kg/day, 54 mg/m2/day), no significant effect on reproductive function and fertility was found. In female rats at doses of 6 or 9 mg/kg/day (36 or 54 mg/m2/day), a decrease in the number of implantations was noted.

At high doses, spermatogenesis is disrupted and inhibited in rats and dogs, and testicular weight decreases in dogs and baboon monkeys.

Side effects and overdose

Ketonal injections, the instructions for use warn about this, can cause serious negative side reactions of the body from various systems of the human body. You should carefully read the manufacturer's warnings before using the product for symptomatic treatment.

The most common side effects are insomnia, depression, and asthenia. Nervous system disorders may be accompanied by headaches and increased weakness. Also, after taking the medicine, dyspeptic disorders often occur.

An overdose of ketoprofen poses a health risk. Higher doses may cause vomiting and abdominal pain. The drug, used once in large quantities, can lead to respiratory depression, convulsions, and loss of consciousness. There are risks of developing renal dysfunction. If an overdose is confirmed, you urgently need to rinse your stomach and take absorbents. Further symptomatic treatment is recommended.

Ketonal injections, which are affordable, interact with many other medications. Therefore, it is strictly forbidden to use them for self-medication. Dosages are prescribed by the doctor depending on the patient’s condition and in accordance with the recommendations of the instructions for use.

Ketoprofen, 50 mg/ml, solution for intravenous and intramuscular administration, 2 ml, 10 pcs.

Undesirable drug combinations

The combined use of ketoprofen with other NSAIDs (including selective cyclooxygenase-2 inhibitors), salicylates in high doses is not recommended, due to the increased risk of gastrointestinal bleeding and ulceration of the gastrointestinal mucosa. Simultaneous use with anticoagulants (heparin, warfarin), antiplatelet agents (ticlopidine, clopidogrel) increases the risk of bleeding. If the use of such a combination is unavoidable, the patient's condition should be carefully monitored.

When used simultaneously with lithium preparations, it is possible to increase the concentration of lithium in the blood plasma up to toxic values. The concentration of lithium in the blood plasma should be carefully monitored and the dose of lithium preparations should be promptly adjusted during and after treatment with NSAIDs.

Increases the hematological toxicity of methotrexate, especially when used in high doses (more than 15 mg per week). The time interval between stopping or starting therapy with ketoprofen and taking methotrexate should be at least 12 hours.

Combinations to use with caution

During therapy with ketoprofen, patients taking diuretics, especially when dehydration develops, have a higher risk of developing renal failure due to a decrease in renal blood flow caused by inhibition of prostaglandin synthesis. Before starting to use ketoprofen in such patients, rehydration measures should be carried out. After starting treatment, it is necessary to monitor kidney function.

Combined use of the drug with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in patients with impaired renal function (with dehydration, elderly patients) can lead to worsening deterioration of renal function, incl. to the development of acute renal failure.

During the first weeks of simultaneous use of ketoprofen and methotrexate at a dose not exceeding 15 mg per week, blood tests should be monitored weekly. In elderly patients or if there are any signs of renal impairment, the study should be performed more frequently.

Combinations to take into account

Ketoprofen may weaken the effect of antihypertensive drugs (beta blockers, ACE inhibitors, diuretics).

Concomitant use with selective serotonin reuptake inhibitors (SSRIs) increases the risk of gastrointestinal bleeding.

Concomitant use with thrombolytics increases the risk of bleeding.

Concomitant use with potassium salts, potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor blockers, NSAIDs, low molecular weight heparins, cyclosporine, tacrolimus and trimethoprim increases the risk of developing hyperkalemia.

When used simultaneously with cyclosporine and tacrolimus, there may be a risk of additive nephrotoxicity, especially in elderly patients.

The use of several antiplatelet drugs (tirofiban, eptifibatide, abciximab, iloprost) increases the risk of bleeding.

Increases the plasma concentration of cardiac glycosides, slow calcium channel blockers, cyclosporine, methotrexate and digoxin.

Ketoprofen may enhance the effect of oral hypoglycemic and some anticonvulsants (phenytoin).

Concomitant use with probenecid significantly reduces the plasma clearance of ketoprofen.

Nonsteroidal anti-inflammatory drugs may reduce the effectiveness of mifepristone. NSAIDs should be started no earlier than 8–12 days after mifepristone is discontinued.

Pharmaceutically incompatible with tramadol solution due to precipitation.

Ketoprofen gel for external use 5% 30 g (Vertex)

Registration Certificate Holder

VERTEX (Russia)

Dosage form

Medicine - Ketoprofen (Ketoprofen-Vertex)

Description

Gel for external use
1 g
ketoprofen 50 mg

30 g - aluminum tubes (1) - cardboard packs. 50 g - aluminum tubes (1) - cardboard packs.

Indications

Symptomatic treatment of painful and inflammatory processes of various origins, including: rheumatoid arthritis and periarthritis; ankylosing spondylitis (ankylosing spondylitis); psoriatic arthritis; reactive arthritis (Reiter's syndrome); osteoarthritis of various localizations; tendinitis, bursitis; myalgia; neuralgia; radiculitis; injuries of the musculoskeletal system (including sports), bruises of muscles and ligaments, sprains, ruptures of ligaments and muscle tendons.

Contraindications for use

Hypersensitivity to ketoprofen; hypersensitivity to salicylates, tiaprofenic acid or other NSAIDs, fenofibrate, UV blockers, fragrances; violation of the integrity of the skin (eczema, weeping dermatitis, open or infected wound); indications in the anamnesis of attacks of bronchial asthma caused by taking NSAIDs and salicylates; history of photosensitivity reactions; exposure to sunlight, incl. indirect sunlight and UV irradiation in a solarium throughout the entire treatment period and for another 2 weeks after stopping treatment; III trimester of pregnancy; children under 15 years of age.

Carefully

Impaired liver and/or kidney function, erosive and ulcerative lesions of the gastrointestinal tract, blood diseases, bronchial asthma, chronic heart failure.

pharmachologic effect

NSAIDs. It has analgesic, anti-inflammatory and anti-edema effects. Inhibits the activity of COX, which leads to inhibition of prostaglandin synthesis. In addition, ketoprofen inhibits lipoxygenase, bradykinin synthesis, stabilizes lysosomal membranes and prevents the release of enzymes involved in the inflammatory process.

Ketoprofen does not have a negative effect on the condition of articular cartilage.

Drug interactions

Since the concentration of ketoprofen in the blood plasma is extremely low, symptoms of interaction with other drugs (similar symptoms with systemic use) are possible only with frequent and prolonged use.

The simultaneous use of other topical products containing ketoprofen or other NSAIDs is not recommended.

Simultaneous administration of acetylsalicylic acid reduces the degree of binding of ketoprofen to plasma proteins.

Ketoprofen reduces the excretion of methotrexate and increases its toxicity.

Patients taking coumarin-containing anticoagulant drugs are advised to undergo treatment under medical supervision.

Dosage regimen

Apply externally 2-3 times/day.

The duration of treatment without consulting a doctor should not exceed 14 days.

Side effect

Allergic reactions: very rarely - angioedema, anaphylaxis.

From the skin and subcutaneous fat: infrequently - erythema, itching, burning, eczema, mild transient dermatitis; rarely - urticaria, rash, photosensitivity, bullous dermatitis, purpura, erythema multiforme, lichenoid dermatitis, skin necrosis, Stevens-Johnson syndrome; very rarely - a single case of severe contact dermatitis (due to poor hygiene and insolation), a single case of severe generalized photodermatitis, toxic epidermal necrolysis.

From the respiratory system: very rarely - asthmatic attacks (as a variant of an allergic reaction).

From the urinary system: very rarely - deterioration of renal function in patients with chronic renal failure.

special instructions

It is necessary to avoid contact of this product with the eyes, the skin around the eyes, and mucous membranes.

Ketoprofen can be used externally in combination with oral administration. The total daily dose, regardless of the dosage form, should not exceed 200 mg.

To reduce the risk of developing photosensitivity, it is recommended to protect skin areas treated with ketoprofen with clothing from exposure to ultraviolet radiation throughout the entire treatment period and for another 2 weeks after stopping use of the gel.

Do not use as occlusive dressings.

Use during pregnancy and breastfeeding

Restrictions during pregnancy - Contraindicated. Restrictions when breastfeeding - Contraindicated.

Use is contraindicated in the third trimester of pregnancy. Use in the first and second trimesters is possible in cases where the expected benefit of therapy for the mother outweighs the potential risk for the fetus.

Use during lactation (breastfeeding) is not recommended.

Use for renal impairment

Restrictions in case of impaired renal function - With caution. Use with caution in case of impaired renal function.

Use for liver dysfunction

Restrictions in case of liver dysfunction - With caution. Use with caution in case of liver dysfunction.

Use in elderly patients

Restrictions for elderly patients - Use with caution. Use with caution in elderly patients.

Use in children

Restrictions for children - Contraindicated. Contraindicated: children under 15 years of age.

Terms of sale

The drug is approved for use as a means of OTC.